Featured Research

from universities, journals, and other organizations

The Fragile X Syndrome Protein As RNA Distribution Hub

Date:
February 6, 2003
Source:
University Of Pennsylvania Medical Center
Summary:
The process of turning genes into protein makes the insides of cells terribly crowded and complicated places. Signals tell machinery to transcribe the DNA of genes into messenger RNA (mRNA) whose translation into protein has to be coordinated with everything else that is happening within the cell. Fortunately, there are RNA binding proteins to organize mRNAs. These proteins are so critical that the loss of one particular RNA binding protein, FMRP, leads to Fragile X syndrome, the most common inherited forms of mental retardation.

Philadelphia, PA – The process of turning genes into protein makes the insides of cells terribly crowded and complicated places. Signals tell machinery to transcribe the DNA of genes into messenger RNA (mRNA) whose translation into protein has to be coordinated with everything else that is happening within the cell. Fortunately, there are RNA binding proteins to organize mRNAs. These proteins are so critical that the loss of one particular RNA binding protein, FMRP, leads to Fragile X syndrome, the most common inherited forms of mental retardation.

Researchers based at the University of Pennsylvania School of Medicine invented a technique called Antibody Positioned RNA Amplification (APRA) to determine the identity of RNA molecules associated with RNA binding proteins. Their findings on FMRP, presented in the February 6th issue of the journal Neuron, further define the complex basis of Fragile X syndrome.

Fragile X syndrome is the most common inherited cause of mental retardation in both men and women. The disorder causes mental abnormalities that range from slight learning disabilities to severe mental retardation. The syndrome is caused by a mutation in what has been termed the Fragile X mental retardation-1 (Fmr1) gene, which encodes FMRP, the Fragile X mental retardation protein.

"RNA-binding proteins regulate all aspects of RNA synthesis, such as mRNA transcription, splicing and editing, as well as translation of mRNA into protein," said James Eberwine, PhD, professor in Penn's Department of Pharmacology. "The mRNAs held by FMRP encode for proteins that assist in transmitting signals within the brain. FMRP provides cellular mRNA traffic control, and moves selected mRNAs to sites where they can be translated. How FMRP knows where to move these mRNAs and how these mRNAs are released from FMRP is unclear at present."

To study how RNA binding proteins such as FMRP function, Eberwine and his colleagues developed a technique to identify specific mRNAs associated with a particular binding protein. At its basis, APRA enables researchers to analyze an RNA binding protein's cargo on a genome-wide basis.

In practice, APRA works a bit like a homing beacon attached to a photocopier: Eberwine connected an antibody that specifically binds to FMRP to a DNA molecule that can bind to the RNA near the FMRP protein. In the presence of enzymes, the DNA molecule helps copy these RNAs into cDNA (a term for DNA made from RNA).

After it is synthesized, the cDNA is amplified into hundreds of thousands of RNA molecules by an amplification procedure also developed in the Eberwine lab a few years ago. These amplified RNA molecules can be screened against a microarray to identify their corresponding genes. In this bridging of genomics (the study of the genome) and proteomics (global analysis of proteins), the specificity of the antibody's attraction to FMRP induces the specificity of the RNA analysis. Given the nature of Fragile X syndrome – and the fact that FMRP is found only in the tissues of the central nervous system – the researchers were encouraged to find that among the FMRP's cargo are mRNAs encoding proteins involved in transmitting signals between neurons and in neuron maturation.

As a research tool, the researchers believe that APRA analysis has great potential for researchers who want to target specific RNA binding proteins for analysis. Given its specificity, ARPA can track down RNA binding proteins that are only found in certain tissues and examine those proteins under varying physiological conditions or disease states.

"In that sense, APRA could mean to RNA studies as much as DNA and RNA amplification techniques have meant to studying the genome," said Eberwine. "It is also part of the growing frontier of molecular biology – somewhere between genomics and proteomics is the interplay of RNA with RNA-binding proteins."

Researchers also involved in these findings include: lead author Kevin Miyashiro of Penn's Department of Pharmacology; Andrea Beckel-Mitchener, T. Patrick Purk, Ivan Jeanne Wieler, Willam T. Greenough, of the Beckman Institute at the University of Illinois; Lei Liu of the W.M. Keck Center for Comparative and Functional Genomics at the University of Illinois; Salvatore Carbonetto of the Centre for Neuroscience Research at McGill University; and Kevin G. Becker and Tanya Barret of the DNA Array Unit of the National Institute on Aging.

This research was funded through grants from the National Institute on Aging and the National Institute of Mental Health.


Story Source:

The above story is based on materials provided by University Of Pennsylvania Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

University Of Pennsylvania Medical Center. "The Fragile X Syndrome Protein As RNA Distribution Hub." ScienceDaily. ScienceDaily, 6 February 2003. <www.sciencedaily.com/releases/2003/02/030206075822.htm>.
University Of Pennsylvania Medical Center. (2003, February 6). The Fragile X Syndrome Protein As RNA Distribution Hub. ScienceDaily. Retrieved April 18, 2014 from www.sciencedaily.com/releases/2003/02/030206075822.htm
University Of Pennsylvania Medical Center. "The Fragile X Syndrome Protein As RNA Distribution Hub." ScienceDaily. www.sciencedaily.com/releases/2003/02/030206075822.htm (accessed April 18, 2014).

Share This



More Health & Medicine News

Friday, April 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

'Holy Grail' Of Weight Loss? New Find Could Be It

'Holy Grail' Of Weight Loss? New Find Could Be It

Newsy (Apr. 18, 2014) In a potential breakthrough for future obesity treatments, scientists have used MRI scans to pinpoint brown fat in a living adult for the first time. Video provided by Newsy
Powered by NewsLook.com
Little Progress Made In Fighting Food Poisoning, CDC Says

Little Progress Made In Fighting Food Poisoning, CDC Says

Newsy (Apr. 18, 2014) A new report shows rates of two foodborne infections increased in the U.S. in recent years, while salmonella actually dropped 9 percent. Video provided by Newsy
Powered by NewsLook.com
Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. Video provided by Newsy
Powered by NewsLook.com
Obama: 8 Million Healthcare Signups

Obama: 8 Million Healthcare Signups

AP (Apr. 17, 2014) President Barack Obama gave a briefing Thursday announcing 8 million people have signed up under the Affordable Care Act. He blasted continued Republican efforts to repeal the law. (April 17) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins